Working memory and school readiness in preschool children with sickle cell disease compared to demographically matched controls.

Children diagnosed with sickle cell disease (SCD) are at risk of the development of neurobehavioural problems early in life. Specific impairments in executive function skills, including working memory, have been documented in school-aged children with SCD. These executive skills are known to strongly contribute to early academic skills and preparedness for entering kindergarten. This study examined working memory and school readiness in preschool children with SCD compared to a healthy control group matched for race, sex and parent education. A total of 84 patients diagnosed with SCD (61.9% haemoglobin [Hb]SS/HbSß0 -thalassaemia) and 168 controls completed testing. The mean (SD) ages of patients and controls at testing were 4.53 (0.38) and 4.44 (0.65) years respectively. The SCD group performed worse than controls on measures of executive function, working memory and school readiness (p < 0.01; Cohen's D range: 0.32-0.39). Measures of working memory were associated with school readiness after accounting for early adaptive development. Multiple linear regression models among patients diagnosed with SCD revealed that college education of the primary caregiver was positively associated with school readiness (p < 0.001) after controlling for sex, genotype, age and early adaptive development. These results highlight the need to implement school readiness interventions in young children diagnosed with SCD emphasising executive function skills.

Maternal Plasma 25-Hydroxyvitamin D during Gestation Is Positively Associated with Neurocognitive Development in Offspring at Age 4-6 Years.

BACKGROUND: Vitamin D is critical to embryonic neuronal differentiation and other developmental processes that may affect future neurocognitive function. However, observational studies have found inconsistent associations between gestational vitamin D and neurocognitive outcomes. OBJECTIVES: We examined the association of gestational 25-hydroxyvitamin D [25(OH)D] with children's IQ at 4-6 y, and explored whether associations differed by race. METHODS: This study used data from the CANDLE (Conditions Affecting Neurocognitive Development and Learning in Early Childhood) cohort. Between 2006 and 2011, CANDLE recruited 1503 women in their second trimester of healthy singleton pregnancies. Inclusion criteria for this analysis were gestation of ≥34 wk and availability of 25(OH)D and IQ data. Associations between second-trimester 25(OH)D plasma concentration and Stanford-Binet IQ scores in offspring at 4-6 y were examined using multivariable linear regression; interaction terms were used to explore possible effect modification by race. RESULTS: Mean ± SD 25(OH)D concentration among 1019 eligible dyads was 21.6 ± 8.4 ng/mL, measured at a mean ± SD gestational age of 23.0 ± 3.0 wk. Vitamin D deficiency [25(OH)D < 20 ng/mL] was observed in 45.6%. Maternal 25(OH)D differed by race with a mean ± SD of 19.8 ± 7.2 ng/mL in Blacks sand 25.9 ± 9.3 ng/mL in Whites ( P  < 0.001). In adjusted models a 10-ng/mL increase in 25(OH)D was associated with a 1.17-point higher Full Scale IQ (95% CI: 0.27, 2.06 points), a 1.17-point higher Verbal IQ (95% CI: 0.19, 2.15 points), and a 1.03-point higher Nonverbal IQ (95% CI: 0.10, 1.95 points). We observed no evidence of effect modification by race. CONCLUSIONS: Second-trimester maternal 25(OH)D was positively associated with IQ at 4-6 y, suggesting that gestational vitamin D status may be an important predictor of neurocognitive development. These findings may help inform prenatal nutrition recommendations and may be especially relevant for Black and other dark-skinned women at high risk of vitamin D deficiency.

"Nobody Will Tell You. You've Got to Ask!": An Examination of Patient-Provider Communication Needs and Preferences among Black and White Women with Early-Stage Breast Cancer.

Patient-provider communication is a critical component of healthcare and is associated with treatment quality and outcomes for women with breast cancer. This qualitative study examines similarities and differences in patient perspectives of communication needs between Black and White breast cancer survivors. We conducted four focus groups (N = 28) involving women with early-stage breast cancer on adjuvant endocrine therapy (AET), stratified by race and length of time on AET (< 6 months and >6 months). Each group was moderated by a race-concordant moderator and analyzed by emergent themes. Participants expressed common patient-provider communication needs, namely increased sensitivity from oncologists during the initial cancer diagnosis, personalized information to facilitate treatment decisions, emotional support during the transition from active treatment to maintenance, and rapid provider responses to mobile app-based queries. Communication differences by race also emerged. Black women were less likely than White women to describe having their informational needs met. White women praised longstanding relationships with providers, while Black women shared personal stories of disempowered interactions and noted the importance of patient advocates. White women more often reported privacy concerns about technology use. Unlike White women, Black women reported willingness to discuss sensitive topics, both online and offline, but believed those discussions made their providers feel uncomfortable. Early-stage breast cancer patients on AET, regardless of race, have similar needs for patient-centered communication with their oncologists. However, Black women were more likely to report experiencing poorer communication with providers than White women, which may be improved by technology and advocates.

A qualitative exploration of race-based differences in social support needs of diverse women with breast cancer on adjuvant therapy.

OBJECTIVE: Social support is a critical component of breast cancer care and is associated with clinical and quality of life outcomes. Significant health disparities exist between Black and White women with breast cancer. Our study used qualitative methods to explore the social support needs of Black and White women with hormone receptor-positive breast cancer on adjuvant endocrine therapy (AET). METHODS: We conducted four focus group (FG) interviews (N = 28), stratified by race (ie, Black and White) and time on AET. FGs were audiotaped, transcribed, and analyzed according to conventions of thematic analysis. RESULTS: Participants noted the importance of having their informational and emotional social support needs met by friends and family members. White participants reported support provided by others with breast cancer was crucial; Black women did not discuss other survivors as part of their networks. Notably, both White and Black participants used the FG environment to provide experiential social support to each other. CONCLUSIONS: White participants noted that having other breast cancer survivors in their support network was essential for meeting their social support needs. However, Black participants did not reference other breast cancer survivors as part of their networks. Cancer centers should consider reviewing patients' access to experiential support and facilitate opportunities to connect women in the adjuvant phase.

Atherosclerotic cardiovascular disease risk assessment and predictors of statin use in Filipino-American Women.

WHAT IS KNOWN AND OBJECTIVE: Race and gender disparities in the context of appropriate treatment with lipid-lowering therapies do exist. The 2013 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines outlined four groups, three for primary prevention and one for secondary prevention, whom would benefit from statin therapy to target atherosclerotic cardiovascular disease (ASCVD). The application of these recommendations in Filipino women living in the United States is unknown; however, this population is known to have elevated cardiovascular risk. Socio-economic and clinical characteristics that predict statin utilization of this Asian American subgroup need to be explored. METHODS: This was an exploratory analysis of data collected during a cross-sectional study of Filipino-American Women (FAW). The Pooled Cohort equation was used to estimate 10-year ASCVD risk. Bivariate analysis was employed to determine the association between statin treatment and clinical and socio-economic factors. Data were analysed using SAS® 9.4; statistical significance was set at P < 0.05. RESULTS AND DISCUSSION: A total of 384 women (mean age 56.3 years) were included in the original study, and the average 10-year ASCVD risk was 3.5 ± 3.7%. Upon applying the 2013 ACC/AHA guidelines, 97 FAW were categorized into one of the primary prevention groups. Women considered to benefit from a statin based on the guideline criteria but were not prescribed a statin were considered the not statin treated group (n = 55). From the original cohort, 93 FAW reported current statin therapy use and were categorized as statin treated. The clinical characteristics associated with not being statin treated were as follows: untreated blood pressure (P = 0.012), higher diastolic blood pressure (P = 0.015), higher total cholesterol (P < 0.001), higher triglycerides (P = 0.041), higher low-density lipoprotein (P < 0.001) and higher glucose (P = 0.011). The socio-economic factor associated with not being statin treated was having two or more insurance payers (P = 0.005). Overall, this population had a waist circumference and body mass index (BMI) that exceeds guidelines for Asian women (31.5 or 80 cm). WHAT IS NEW AND CONCLUSION: Predictors of statin utilization in FAW are not well documented in the literature. These findings emphasize room for improvement for the prescribing of statins in primary prevention for this study population. Applying culturally appropriate screening strategies to identify cardiovascular risk factors early such as BMI or waist circumference may assist with quantifying patients into one of the statin benefit groups if eligible.

Psychometric evaluation of the nursing child assessment teaching (NCAT) scale in a community-based sample.

The effect of the mother-child relationship on long-term child development has received research attention for decades. Because the quality and quantity of mother-infant interactions have been established as important predictors of the child's development, early identification of areas in the relationship requiring support and intervention is essential for promoting positive child outcomes. The Nursing Child Assessment Teaching Scale (NCAT) is an instrument long used to quantify the quality of interaction in the mother-child relationship during the first 36 months of a child's life. While the NCAT has been shown to be a reliable and valid instrument, limited evidence exists of the theoretical congruence between the Barnard Model it is based on and the NCAT scale. The psychometric properties of the NCAT scale and subscales were examined using item response theory in relation to characteristics of interactions in the Barnard Model using data collected during a clinic visit at 12 months of infant age in a sample of mothers and children (N = 1,121 dyads) from a community-based sample in Shelby County, TN. In this secondary analysis, descriptive statistics, reliabilities, and factor loadings for the NCAT were obtained using confirmatory factor analysis and augmented to form multiple indicators, multiple causes models, linking demographic predictors of the mothers and children to the NCAT subscales. Results supported scale abbreviation and theoretical congruence with the Barnard Model, which may provide researchers and practitioners with a more concise, reliable way of measuring maternal-child interaction in community settings.

Quality of Life and African American Women Who are Family Caregivers: A Literature Review with Implications for Psychiatric Mental Health Advanced Practice Registered Nurses.

PURPOSE: To identify factors affecting the quality of life (QOL) of African American women (AAW) family caregivers of individuals with kidney failure. METHODS: Ferrans' Conceptual Model of QOL provided the framework for this literature review. Included studies were (a) peer- reviewed, (b) published within the last ten years, (c) written in English, and (d) examined QOL of AAW family caregivers. Using CINAHL© and PubMed©, we found 14 studies that described factors associated with these caregivers' QOL. SCOPE: Few studies document the QOL of AAW who are family caregivers, especially in the context of kidney failure. Psychiatric Mental Health Advanced Practice Registered Nurses need to learn about the factors influencing the QOL of these caregivers. RESULTS: No studies were found within the last ten years that explored the QOL of AAW family caregivers of individuals with kidney failure. Findings reflected the QOL of AAW family caregivers in the context of other chronic conditions. Various factors such as stress, insomnia, and employment were linked to an impaired QOL. Implications for practice, research and education for PMH-APRNs are suggested. CONCLUSION: PMH-APRNs are uniquely trained to address many factors that affect the QOL of these caregivers and may provide holistic care aimed at promoting satisfactory QOL for these caregivers.

Maternal and Child Characteristics Associated With Mother-Child Interaction in One-Year-Olds.

Mothers' interactions with their young children have predicted later child development, behavior, and health, but evidence has been developed mainly in at-risk clinical samples. An economically and racially diverse sample of pregnant women who were not experiencing a high-risk pregnancy were recruited to participate in a community-based, longitudinal study of factors associated with child cognitive and social-emotional development during the first 3 years. The purpose of the present analysis was to identify associations between the characteristics of 1125 mothers and their 1-year-olds and the mothers' and children's scores on the Nursing Child Assessment Teaching Scale (NCATS). A multivariable approach was used to identify maternal and child characteristics associated with NCATS scores and to develop prediction models for NCATS total and subscale scores of mothers and children. Child expressive and receptive communication and maternal IQ, marital status, age, and insurance predicted NCATS Mother total score, accounting for 28% of the score variance. Child expressive communication and birth weight predicted the NCATS Child total score, accounting for 4% of variance. Child's expressive communication and mother's IQ and marital status predicted NCATS mother-child total scores. While these findings were similar to reports of NCATS scores in at-risk populations, no previous teams examined all of the mother and child characteristics included in this analysis. These findings support the utility of the NCATS for assessing mother-child interaction and predicting child outcomes in community-based, non-clinical populations. © 2017 Wiley Periodicals, Inc.

Male Caregivers of Persons with End Stage Renal Disease: A Qualitative Study.

This study explored experiences associated with burden, depressive symptoms, and perceived health in six male caregivers of persons with end stage renal disease (ESRD) using qualitative interviews. Analysis employed open coding and analysis to generate codes and categories. Eighty-three percent of the participants reported significant subjective and objective burden. Linkages occurred between sociodemographic characteristics, care recipient attributes, and caregiver-care recipient relationship, and caregivers' experience of burden and depressive symptoms. Findings suggest the need for intervention trials targeting new coping strategies to help improve the well-being of this population.

Male Caregivers of Persons with End Stage Renal Disease: A Literature Review.

This literature review examined burden, depressive symptoms, and perceived health reported by male caregivers of persons with end stage renal disease. These studies suggest that male caregivers often experience negative outcomes. Compared to non-caregivers, male caregivers had higher levels of anxiety and depressive symptoms. Qualitative studies suggest depression is common and associated with conflict between caregiving responsibilities and work, poor caregiver health, and fears about the future outcomes of relatives for whom they provide care. Future research will assist healthcare providers to identify at-risk male caregivers and develop effective interventions to support this understudied caregiver population.

Epigenetic analysis of neurocognitive development at 1 year of age in a community-based pregnancy cohort.

Multiple studies show that molecular genetic changes and epigenetic modifications affect the risk of cognitive disability or impairment. However, the role of epigenetic variation in cognitive development of neurotypical young children remains largely unknown. Using data from a prospective, community-based study of mother-infant pairs, we investigated the association of DNA methylation patterns in neonatal umbilical cord blood with cognitive and language development at 1 year of age. No CpG loci achieved genome-wide significance, although a small number of weakly suggestive associations with Bayley-III Receptive Communication scales were noted. While umbilical cord blood is a convenient resource for genetic analyses of birth outcomes, our results do not provide conclusive evidence that its use for DNA methylation profiling yields epigenetic markers that are directly related to postnatal neurocognitive outcomes at 1 year of age.

Transition from pediatric to adult care in sickle cell disease: perspectives on the family role.

Transition from pediatric to adult care poses challenges for adolescents with sickle cell disease (SCD). This study explored the transition perspectives of adolescents with SCD, their siblings, and caregivers. Focus groups were conducted with 12 African American families. Adolescents, siblings, and caregivers demonstrated awareness of transition and need for disease management responsibility. Siblings' and caregivers' concerns included adolescent medication adherence. Family concerns included leaving the pediatric environment and adult providers' lack of knowledge. Families recommended more transition preparation opportunities. Family members' perspectives are valuable in informing transition planning. Family-focused interventions designed to prepare and support families during transition are necessary.

Early adversity, socioemotional development, and stress in urban 1-year-old children.

OBJECTIVE: To determine demographic, maternal, and child factors associated with socioemotional (SE) problems and chronic stress in 1-year-old children. STUDY DESIGN: This was a prospective, longitudinal, community-based study, which followed mother-infant dyads (n = 1070; representative of race, education, and income status of Memphis/Shelby County, Tennessee) from midgestation into early childhood. Child SE development was measured using the Brief Infant-Toddler Social and Emotional Assessment in all 1097 1-year-olds. Chronic stress was assessed by hair cortisol in a subsample of 1-year-olds (n = 297). Multivariate regression models were developed to predict SE problems and hair cortisol levels. RESULTS: More black mothers than white mothers reported SE problems in their 1-year-olds (32.9% vs 10.2%; P < .001). In multivariate regression, SE problems in blacks were predicted by lower maternal education, greater parenting stress and maternal psychological distress, and higher cyclothymic personality score. In whites, predictors of SE problems were Medicaid insurance, higher maternal depression score at 1 year, greater parenting stress and maternal psychological distress, higher dysthymic personality score, and male sex. SE problem scores were associated with higher hair cortisol levels (P = .01). Blacks had higher hair cortisol levels than whites (P < .001). In the entire subsample, increased hair cortisol levels were associated with higher parenting stress (P = .001), lower maternal depression score (P = .01), lower birth length (P < .001), and greater length at 1 year of age (P = .003). CONCLUSION: Differences in maternal education, insurance, mental health, and early stress may disrupt SE development in children. Complex relationships between hair cortisol level in 1-year-olds and maternal parenting stress and depression symptoms suggest dysregulation of the child's hypothalamic-pituitary-adrenal axis.

The role of prenatal violence exposure in the development of disparities in children's adiposity from birth to middle childhood.

OBJECTIVE: This study examined whether women's exposure to multiple types of violence during childhood and pregnancy was associated with children's BMI trajectories and whether parenting quality moderated those associations. METHODS: A cohort of 1288 women who gave birth between 2006 and 2011 self-reported their exposure to childhood traumatic events, intimate partner violence (IPV), and residential address (linked to geocoded index of violent crime) during pregnancy. Children's length/height and weight at birth and at age 1, 2, 3, 4 to 6, and 8 years were converted to BMI z scores. Observed mother-child interactions were behaviorally coded during a dyadic teaching task. RESULTS: Covariate-adjusted growth mixture models identified three trajectories of children's BMI from birth to 8 years old: Low-Stable (17%), Moderate-Stable (59%), and High-Rising (22%). Children whose mothers experienced more types of IPV during pregnancy were more likely to be in the High-Rising than the Low-Stable (odds ratio [OR] = 2.62; 95% CI: 1.27-5.41) trajectory. Children whose mothers lived in higher crime neighborhoods were more likely to be in the High-Rising than the Low-Stable (OR = 1.11; 95% CI:1.03-1.17) or Moderate-Stable trajectories (OR = 1.08; CI: 1.03-1.13). Main effects of childhood traumatic events and moderation by parenting were not detected. CONCLUSIONS: Maternal experiences of violence during pregnancy increase children's risk for developing overweight, highlighting intergenerational transmission of social adversity in children's health.

Time to establish an international vaccine candidate pool for potential highly infectious respiratory disease: a community's view.

In counteracting highly infectious and disruptive respiratory diseases such as COVID-19, vaccination remains the primary and safest way to prevent disease, reduce the severity of illness, and save lives. Unfortunately, vaccination is often not the first intervention deployed for a new pandemic, as it takes time to develop and test vaccines, and confirmation of safety requires a period of observation after vaccination to detect potential late-onset vaccine-associated adverse events. In the meantime, nonpharmacologic public health interventions such as mask-wearing and social distancing can provide some degree of protection. As climate change, with its environmental impacts on pathogen evolution and international mobility continue to rise, highly infectious respiratory diseases will likely emerge more frequently and their impact is expected to be substantial. How quickly a safe and efficacious vaccine can be deployed against rising infectious respiratory diseases may be the most important challenge that humanity will face in the near future. While some organizations are engaged in addressing the World Health Organization's "blueprint for priority diseases", the lack of worldwide preparedness, and the uncertainty around universal vaccine availability, remain major concerns. We therefore propose the establishment of an international candidate vaccine pool repository for potential respiratory diseases, supported by multiple stakeholders and countries that contribute facilities, technologies, and other medical and financial resources. The types and categories of candidate vaccines can be determined based on information from previous pandemics and epidemics. Each participant country or region can focus on developing one or a few vaccine types or categories, together covering most if not all possible potential infectious diseases. The safety of these vaccines can be tested using animal models. Information for effective candidates that can be potentially applied to humans will then be shared across all participants. When a new pandemic arises, these pre-selected and tested vaccines can be quickly tested in RCTs for human populations.

An alternative approach-combination of lockdown and open in fighting COVID-19 pandemics.

As the COVID-19 pandemic enters its third year and the omicron variant becomes dominant, we propose an alternative strategy for dealing with COVID-19, called hybrid lockdown, that is, the combination of lockdown (the centralized and organized lockdown of the high-risk population) and free mobility (normal mobility) of the low-risk population. Such an approach will enable a country or region, especially with a high population density, to achieve significant prevention and control the effects of the COVID-19 pandemic at the least cost.

Bring the life stages into the domain of basic and clinical pharmacology.

Completely distinct physiological conditions and immune responses exist among different human life stages. Age is not always consistent with the life stage. We proposed to incorporate the concept of the life stages into basic and clinical pharmacology, including clinical trials, drug labels, and drug usage in clinical practice. Life-stage-based medical treatment is the application of medicine according to life stages such as prepuberty, reproductive, and aging. A large number of diseases are life-stage-dependent. Many medications and therapy have shown various age effects but not been recognized as life-stage-dependent. The same dosage and drug applications used in different life stages lead to divergent outcomes. Incorporating life stages in medicine and drug usage will enhance the efficacy and precision of the medication in disease treatment.

Variations of COVID-19 mortality are affected by economic disparities across countries.

BACKGROUND: When the COVID-19 case number reaches a maximum in a country, its capacity and management of health system face greatest challenge. METHODS: We performed a cross-sectional study on data of turning points for cases and deaths for the first three waves of COVID-19 in countries with more than 5000 cumulative cases, as reported by Worldometers and WHO Coronavirus (COVID-19) Dashboard. We compared the case fatality rates (CFRs) and time lags (in unit of day) between the turning points of cases and deaths among countries in different development stages and potential influence factors. As of May 10, 2021, 106 out of 222 countries or regions (56%) reported more than 5000 cases. Approximately half of them have experienced all the three waves of COVID-19 disease. The average mortality rate at the disease turning point was 0.038 for the first wave, 0.020 for the second wave, and 0.023 for wave 3. In high-income countries, the mortality rates during the first wave are higher than that of the other income levels. However, the mortality rates during the second and third waves of COVID-19 were much lower than those of the first wave, with a significant reduction from 5.7% to 1.7% approximately 70%. At the same time, high-income countries exhibited a 2-fold increase in time lags during the second and the third waves compared to the first wave, suggesting that the periods between the cases and deaths turning point extended. High rates in the first wave in developed countries are associated to multiple factors including transportation, population density, and aging populations. In upper middle- and lower middle-income countries, the decreasing of mortality rates in the second and third waves were subtle or even reversed, with increased mortality during the following waves. In the upper and lower middle-income countries, the time lags were about 50% of the durations observed from high-income countries. INTERPRETATION: Economy and medical resources affect the efficiency of COVID-19 mitigation and the clinical outcomes of the patients. The situation is likely to become even worse in the light of these countries' limited ability to combat COVID-19 and prevent severe outcomes or deaths as the new variant transmission becomes dominant.

Intergenerational Transmission of Effects of Women's Stressors During Pregnancy: Child Psychopathology and the Protective Role of Parenting.

Objective: Experiences of stress and adversity, such as intimate partner violence, confer risk for psychiatric problems across the life span. The effects of these risks are disproportionately borne by women and their offspring-particularly those from communities of color. The prenatal period is an especially vulnerable period of fetal development, during which time women's experiences of stress can have long-lasting implications for offspring mental health. Importantly, there is a lack of focus on women's capacity for resilience and potential postnatal protective factors that might mitigate these intergenerational risks and inform intervention efforts. The present study examined intergenerational associations between women's prenatal stressors and child executive functioning and externalizing problems, testing maternal parenting quality and child sex as moderators, using a large, prospective, sociodemographically diverse cohort. Methods: We used data from 1,034 mother-child dyads (64% Black, 30% White) from the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) pregnancy cohort within the ECHO PATHWAYS consortium. Women's prenatal stressors included stressful life events (pSLE) and intimate partner violence (pIPV). Measures of child psychopathology at age 4-6 included executive functioning and externalizing problems. Parenting behaviors were assessed by trained observers, averaged across two sessions of mother-child interactions. Linear regression models were used to estimate associations between women's prenatal stressors and child psychopathology, adjusting for confounders and assessing moderation effects by maternal parenting quality and child sex. Results: Women's exposures to pSLE and pIPV were independently associated with child executive functioning problems and externalizing problems in fully-adjusted models. Maternal parenting quality moderated associations between pSLE and both outcomes, such that higher parenting quality was protective for the associations between women's pSLE and child executive functioning and externalizing problems. No moderation by child sex was found. Discussion: Findings from this large, sociodemographically diverse cohort suggest women's exposures to interpersonal violence and major stressful events-common for women during pregnancy-may prenatally program her child's executive functioning and externalizing problems. Women's capacity to provide high quality parenting can buffer this intergenerational risk. Implications for universal and targeted prevention and early intervention efforts to support women's and children's wellbeing are discussed.

Mortality in Four Waves of COVID-19 Is Differently Associated with Healthcare Capacities Affected by Economic Disparities.

BACKGROUND: The greatest challenges are imposed on the overall capacity of disease management when the cases reach the maximum in each wave of the pandemic. METHODS: The cases and deaths for the four waves of COVID-19 in 119 countries and regions (CRs) were collected. We compared the mortality across CRs where populations experience different economic and healthcare disparities. FINDINGS: Among 119 CRs, 117, 112, 111, and 55 have experienced 1, 2, 3, and 4 waves of COVID-19 disease, respectively. The average mortality rates at the disease turning point were 0.036, 0.019. 0.017, and 0.015 for the waves 1, 2, 3, and 4, respectively. Among 49 potential factors, income level, gross national income (GNI) per capita, and school enrollment are positively correlated with the mortality rates in the first wave, but negatively correlated with the rates of the rest of the waves. Their values for the first wave are 0.253, 0.346 and 0.385, respectively. The r value for waves 2, 3, and 4 are -0.310, -0.293, -0.234; -0.263, -0.284, -0.282; and -0.330, -0.394, -0.048, respectively. In high-income CRs, the mortality rates in waves 2 and 3 were 29% and 28% of that in wave 1; while in upper-middle-income CRs, the rates for waves 2 and 3 were 76% and 79% of that in wave 1. The rates in waves 2 and 3 for lower-middle-income countries were 88% and 89% of that in wave 1, and for low-income countries were 135% and 135%. Furthermore, comparison among the largest case numbers through all waves indicated that the mortalities in upper- and lower-middle-income countries is 65% more than that of the high-income countries. INTERPRETATION: Conclusions from the first wave of the COVID-19 pandemic do not apply to the following waves. The clinical outcomes in developing countries become worse along with the expansion of the pandemic.